The objectives of this research involve the synthesis and characterization of synthetic analogs of various heme proteins. The reactions of interest include (1) ligand binding to the heme, (2) oxygen activation and hydrocarbon oxidation by metalloporphyrins, and (3) the interactions between porphyrins as redox partners in organized media. These enzymes are relevant to cardiovascular functioning; to drug, hormone, and exobiotic metabolism; to oxidant detoxification and substrate oxidation; and to biological electron transfer and photosynthesis. These studies are directed towards an understanding of the molecular mechanisms of these protein reactions in closely related model metalloporphyrins and oligopeptide-heme complexes. Proposed work includes the synthesis of oligopeptide-heme complexes as totally synthetic heme proteins; further studies of molecular recognition and substrate specificity on the basis of shape, polarity, charge and hydrogen bonding; chemical, photochemical, and photocatalytic generation of highly oxidized iron porphyrin complexes; and the synthesis of bis(porphyrin) metal complexes. A systematic examination of the effects of amino acid residues flanking a coordinating histidine have revealed the substantial effect of hydrophobic interactions in oligopeptide binding to heme: non-polar alpha-helix forming residues increase binding by nearly 105. In work with synthetic metalloporphyrins, we are developing superstructured macrocycles as shape, size, and polarity selective oxidation catalysts. Our "bis-pocket" porphyrins provide steric or polar pockets on both faces of the macrocycle, produce very stable Fe-O2 complexes, and prevent oxidative degradation. The sterically-protected pockets can induce shape selective oxidations and catalyze terminal hydroxylation and epoxidation. Our exploration of the photochemistry of metalloporphyrins has created a new route to the formation of metal-oxo complexes. Exploitation of this discovery may permit observation of intermediates of heme monooxygenases. Continuation of our efforts in these areas should lead to a quantitative understanding of the influences which modulate ligand binding in protein environments, to further characterization and isolation of high oxidation state heme protein intermediates, to a closer understanding of substrate selectivity and regiospecificity by monooxygenases, and to basic knowledge about the interactions in kappa-overlapping systems such as the photosynthetic reaction center. Finally, the use of protein microencapsulation will be explored. Ultrasonic irradiation of cysteine-containing proteins (e.g., serum albumin and hemoglobin) creates micron-sized spheres that can be either gas-filled or non-aqueous liquid-filled. Development of proteinaceous microspheres as artificial erythrocytes for O2 transport, as contrast agents for magnetic resonance imaging, and as spin-label probes for in vivo O2 and temperature profiling is in progress.